Classical and noncanonical functions of miRNAs in cancers

Dragomir, Mihnea P.; Knutsen, Erik; Calin, George A.

doi:10.1016/j.tig.2021.10.002

Cited by 99 publications

(55 citation statements)

References 162 publications

(177 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, some interactions lead to an increase in translation of the target transcript, as exemplified by the ability of miR-122 to stabilize and enhance translation of the hepatitis C virus RNA genome through binding to a 5′ UTR element (reviewed in [ 2 ]). miRNAs can also perform other functions by binding to DNA and directly regulating gene transcription, by acting as ‘sponges’ in miRNA-ncRNA-mRNA regulatory circuits, and by binding to and influencing the activity of proteins distinct from those involved in the canonical post-transcriptional silencing pathway (reviewed in [ 3 ]). Disruption of the complex mechanisms that govern miRNA expression/activity contributes to many diseases, including cancer [ 3 ].…”

Section: Genomic Organization Of the Mir-200 Familymentioning

confidence: 99%

“…miRNAs can also perform other functions by binding to DNA and directly regulating gene transcription, by acting as ‘sponges’ in miRNA-ncRNA-mRNA regulatory circuits, and by binding to and influencing the activity of proteins distinct from those involved in the canonical post-transcriptional silencing pathway (reviewed in [ 3 ]). Disruption of the complex mechanisms that govern miRNA expression/activity contributes to many diseases, including cancer [ 3 ].…”

Section: Genomic Organization Of the Mir-200 Familymentioning

confidence: 99%

See 1 more Smart Citation

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cavallari

Ciccarese

Sharova

et al. 2021

Cancers

View full text Add to dashboard Cite

The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.

show abstract

Section: Genomic Organization Of the Mir-200 Familymentioning

confidence: 99%

Section: Genomic Organization Of the Mir-200 Familymentioning

confidence: 99%

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cavallari

Ciccarese

Sharova

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…As canonical function of miRNA species involves the target hybridisation with the seed sequence, 5' modifications can easily modify the target and the function of the isomiR compared to its Ref-miR, as is supported by many studies (49)(50)(51)(52). Nevertheless, other isomiR types, especially the highly diverse group of 3' isomiR, can also be of functional importance, as the 3' end composition affects Argonaute 2 affinity for canonical miRNA function (53), and non-canonical functions are more and more described for miRNA species (40,41) including in the nucleus, where our analysis shows specific enrichment of isomiR species and types. Functional importance of 3' modifications is further supported by previous studies (37)(38)(39).…”

Section: Discussionmentioning

confidence: 92%

“…Consistently in the senescence dataset, we observed 595 isomiRs being uniquely differentially expressed in freshly isolated samples compared to those adjusted to static cell culture conditions (Fig 5C). Moreover, beyond the compartment-specific differential expression, we observed that the isomiR type distribution was significantly different between the nucleus-enriched and cytosol-enriched species (p <1.80e-07 in X² test, Fig 5D ), suggesting differential regulation of isomiR sequences, as nuclear-enriched isomiRs may be implicated in non-canonical regulatory functions in the nucleus (40,41).…”

Section: Isomirs Allow For In-depth Exploration Of Specific Biological Conditionsmentioning

confidence: 91%

isomiRs-specific differential expression is the rule, not the exception: Are we missing hundreds of species in microRNA analysis?

Schmauch

Laitinen

Turunen

et al. 2021

Preprint

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are small RNA molecules that act as regulators of gene expression through targeted mRNA degradation. They are involved in many biological and pathophysiological processes and are widely studied as potential biomarkers and therapeutics agents for human diseases, including cardiovascular disorders. Recently discovered isoforms of miRNAs (isomiRs) exist in high quantities and are very diverse. Despite having few differences with their corresponding reference miRNAs, they display specific functions and expression profiles, across tissues and conditions. However, they are still overlooked and understudied, as we lack a comprehensive view on their condition-specific regulation and impact on differential expression analysis. Here, we show that isomiRs can have major effects on differential expression analysis results, as their expression is independent of their host miRNA genes or reference sequences. We present two miRNA-seq datasets from human umbilical vein endothelial cells, and assess isomiR expression in response to senescence and compartment-specificity (nuclear/cytosolic) under hypoxia. We compare three different methods for miRNA analysis, including isomiR-specific analysis, and show that ignoring isomiRs induces major biases in differential expression. Moreover, isomiR analysis permits higher resolution of complex signal dissection, such as the impact of hypoxia on compartment localization, and differential isomiR type enrichments between compartments. Finally, we show important distribution differences across conditions, independently of global miRNA expression signals. Our results raise concerns over the quasi exclusive use of miRNA reference sequences in miRNA-seq processing and experimental assays. We hope that our work will guide future isomiR expression studies, which will correct some biases introduced by golden standard analysis, improving the resolution of such assays and the biological significance of their downstream studies.

show abstract

“…MicroRNAs (miRNAs) are small (18-25 nucleotides in length), non-coding endogenous RNAs that act as key regulators of gene expression. Numerous studies have demonstrated the dysregulation of miRNA expression in human cancers through various mechanisms (10,11). miR-877-5p has been proved to a tumor suppressor that is involved in the development of several types of cancer, including hepatocellular carcinoma (HCC) (12), non-small cell lung cancer (NSCLC) (13), gastric cancer (14) and cervical cancer (15).…”

Section: Introductionmentioning

confidence: 99%

CircPIK3C2A Facilitates the Progression of Glioblastoma via Targeting miR-877-5p/FOXM1 Axis

et al. 2021

View full text Add to dashboard Cite

Glioblastoma is a rare yet lethal type of tumor that poses a crucible for the medical profession, owing to its rapid proliferation and invasion resulting in poor prognosis. Circular RNAs (circRNAs), a subclass of regulatory RNAs, are implicated in the regulation of cancerous progression. This study aims to investigate the roles and underlying mechanism of circPIK3C2A in regulating proliferation and invasion of glioblastoma. qRT-PCR assays showed that the expression level of circPIK3C2A was aberrantly higher in glioblastoma cell lines, in comparison with that in normal glia cells. The ectopic expression of circPIK3C2A promoted the proliferation, invasion and clonal formation of glioblastoma cells, while circPIK3C2A loss-of-function exerted exactly the opposite biological effects on the cells. The construction of subcutaneous xenograft tumor model in nude mice indicated that circPIK3C2A loss-of-function effectively diminished tumor load in vivo and prolonged the survival time of tumor-bearing animals. Luciferase reporter assay confirmed the interaction among circPIK3C2A/miR-877-5p and FOXM1. CircPIK3C2A function as competitive endogenous RNA via sponging miR-877-5p through certain binding sites, thereby modulating the expression of FOXM1. Our results collectively indicate that circPIK3C2A functions as ceRNA by mediating miR-877-5p/FOXM1 axis, providing a novel perspective of applying CircPIK3C2A in the clinical intervention of glioblastoma in the future.

show abstract

Classical and noncanonical functions of miRNAs in cancers

Cited by 99 publications

References 162 publications

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

isomiRs-specific differential expression is the rule, not the exception: Are we missing hundreds of species in microRNA analysis?

CircPIK3C2A Facilitates the Progression of Glioblastoma via Targeting miR-877-5p/FOXM1 Axis

Contact Info

Product

Resources

About